Pediatric Tuberculosis Immunology
Deborah Lewinsohn, MDAssociate Professor
Pediatrics; Molecular Microbiology & Immunology, VGTI
Global Burden of Tuberculosis
Persons Infected 2 Billion
Estimated Cases 2003Adults: 8,800,000Children: 250,000
Estimated Deaths 2003Adults: 1,700,000Children: 100,000
WHO: The World Health Report 2007
Natural History of M. tuberculosis Infection
Acute Chronic
Bac
teri
al L
oad
Innate (TST-)Adaptive (TST+)
1° ProgressiveDisease (<5% vs. 50-80%)
ReactivationDisease (5-10%)
Persistent Infection(90% vs 5-50%)
Adapted from: Henry Boom, TBRU, CWRU
Lewinsohn2 Research Group
Current Pediatric projects:• Mtb-infection of DC (Justin Jin)• Effect of age on NHP DC function (Sue Smyk-
Pearson, Lynne Swarbrick)• T cell immunity in Mtb-infected Ugandan
children (Megan Null, Melissa Nyendak, Lynne Swarbrick).
• Mtb-reactive thymoctyes (Marielle Gold, Sue Smyk-Pearson).
Dawn Nolt
• Antigen processing and presentation of Mtbto present to CD8+ T cells.– Trafficking of Class Ia and Class Ib (HLA-E) to
and from the Mtb phagosome (Dawn Nolt, Jake Delepine.
– Trafficking of Mtb (Melanie Hariff, Colleen Noviello, Joel Weekley).
Lewinsohn2 Research Group
Current Pediatric-related projects:• CD8 epitope discovery project (Melissa Nyendak,
Lynne Swarbrick, Megan Null, Meghan Cansler, Jake Delepine, Todd Vogt).
• IL-10 producing Mtb-specific T cells (Justin Jin, Stefania Cerri)
Lewinsohn2 Research Group
Other projects:• Antigen cross-presentation inhibited by Mtb
(Colleen Noviello, Marielle Gold).• Aeras Phase I trial site for TB vaccines.
CTSA Collaborations
• Melissa Nyendak (KL-12 –funded): study of T cell immunity in Ugandan children and adults.
• CD8 epitope discovery: enrollment of adults with TB in San Francisco (inter CTSA collaboration).
• AERAS phase I site for TB vaccines.
Other Collaborators
• Tomi Mori and Shannon McWeeney• VGTI (Janko Nickolich-Zugich)• MMI• CWRU, TBRU (Henry Boom).
Future work Pediatric TB immunology
• Continued focus on TB immunity in Ugandan children, Mtb-specific thymocytes.
• Expanded work in validation of CD8 epitopes in Ugandan children.
• Expanded work in innate Treg immunity and TB.
Potential additional CTSA collaborations
• Normal human subjects program?– IRB support– Normal human serum?– Leukapheresis of normal donors and Mtb-
infected individuals?– Thymus collection?
• Pediatric biostatistics support?